This proposal for a K24 award (competing renewal) is to support the candidate, Roy M. Gulick, MD, MPH, Professor of Medicine and Director of the Cornell HIV Clinical Trials Unit, as an HIV/AIDS clinical researcher, leader, and mentor. Dr. Gulick has conducted clinical trials in HIV-infected patients since 1989, with a focus on antiretroviral studies. His long-term career goals are to develop and lead high-quality research to address clinically important questions in the treatment of patients with HIV/AIDS and to teach and mentor trainees to help develop their careers as clinical investigators. The specific aims of the proposal are: (1) to compare two initial antiretroviral regimens in treatment-na[unreadable]ve patients with HIV infection: zidovudine/lamivudine/abacavir plus tenofovir (a quadruple-nucleoside regimen) vs. a standard regimen of 2 nucleoside analogues plus efavirenz (2) to determine CD4 cell count changes and immune responses with the new CCR5 antagonist, maraviroc in subjects on antiretroviral therapy with suboptimal CD4 cell responses despite sustained virologic suppression (3) to mentor medical students, internal medicine residents, infectious disease fellows, and junior faculty at Weill Medical College of Cornell University as well as to train and mentor developing investigators in Haiti and to assist in the planning, design and conduct of antiretroviral studies in Haiti The specific aims will be accomplished by designing, conducting, and analyzing clinical trials of antiretroviral therapies, playing a leadership role in the NIH-funded AIDS Clinical Trials Group (ACTG) as Principal Investigator of the Cornell unit and as Chairman of the Optimization of Antiretroviral Therapy Committee, and by teaching and mentoring trainees from Weill Medical College of Cornell University and Haiti. Clinical trials of novel strategies and agents will improve the treatment of HIV-infected patients, both in the United States and the developing world. Effective training and mentoring will help develop future clinical investigators both in the United States and in developing countries, such as Haiti.